ClinVar Miner

Submissions for variant NM_000525.4(KCNJ11):c.844G>A (p.Glu282Lys)

gnomAD frequency: 0.00003  dbSNP: rs267607196
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000009223 SCV000247655 pathogenic Hyperinsulinemic hypoglycemia, familial, 2 2015-01-05 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000763231 SCV000893864 likely pathogenic Permanent neonatal diabetes mellitus; Diabetes mellitus, transient neonatal, 3; Hyperinsulinemic hypoglycemia, familial, 2; Type 2 diabetes mellitus; Maturity-onset diabetes of the young type 13 2018-10-31 criteria provided, single submitter clinical testing
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic RCV002226646 SCV002505436 uncertain significance Maturity onset diabetes mellitus in young criteria provided, single submitter research Mutations in KCNJ11 gene can cause decreased production and secretion of insulin. This can lead to MODY which may be responsive to oral sulfonylureas. It is also associated with Neonatal Diabetes. However, no sufficient evidence is found to ascertain the role of rs267607196 variant in MODY yet.
Baylor Genetics RCV003466841 SCV004198053 likely pathogenic Type 2 diabetes mellitus 2024-02-14 criteria provided, single submitter clinical testing
Invitae RCV003555984 SCV004295358 likely pathogenic not provided 2023-12-30 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 282 of the KCNJ11 protein (p.Glu282Lys). This variant is present in population databases (rs267607196, gnomAD 0.004%). This missense change has been observed in individuals with autosomal recessive diffuse or paternally inherited focal hyperinsulinism (PMID: 17114887, 33762279). ClinVar contains an entry for this variant (Variation ID: 8686). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt KCNJ11 protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects KCNJ11 function (PMID: 17956278, 19357197). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
OMIM RCV000009223 SCV000029441 pathogenic Hyperinsulinemic hypoglycemia, familial, 2 2009-07-01 no assertion criteria provided literature only

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